Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with ?-D-mannuronic acid (M2000)

Background & objectives: To examine ?-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ?-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ?-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ?-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ?-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ?-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ?-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management

Diagnosis of a Case of Hepatotoxicity Due to Drugs and Herbal Supplements in a Hospital in Pasto, Colombia

The liver is a crucial organ in metabolism, and some substances can induce toxic hepatitis with high morbidity and mortality. Chemical and drug-induced liver disease is a diagnostic and therapeutic challenge since it requires extension studies to rule out other entities. We present the case of a 51-year-old female patient without underlying comorbidities, admitted due to symptoms of two-day evolution consisting of progressive jaundice, diarrheal episodes without acholia, or any other additional manifestation. Her condition was caused by the intake of nimesulide, two tablets a day for two days, for pain secondary to a mandibular cyst diagnosed in previous days. During her admission to the emergency room, the patient described chronic consumption of Herbalife® products daily for four years. She presented with elevated transaminases, prolonged prothrombin time (PT), and direct hyperbilirubinemia. Infectious and immunological diseases were ruled out. We decided to start antibiotic and vitamin K coverage. Finally, and by exclusion, a liver biopsy suggested an inflammatory process compatible with drug-induced hepatitis. The woman evolved favorably when the medication and dietary supplement were discontinued. In conclusion, this case constitutes an initial point in advancing research into hepatotoxicity by shared mechanisms of various substances simultaneously, such as what happened to the patient with the parallel use of Herbalife® and nimesulide.

El hígado es un órgano crucial en el metabolismo y algunas sustancias pueden inducir hepatitis toxica con alta morbimortalidad. La enfermedad hepática inducida por sustancias químicas y medicamentos es un desafío tanto diagnostico como terapéutico, puesto que requiere la realización de estudios de extensión para descartar otras entidades. A continuación se presenta el caso de una paciente femenina de 51 años sin comorbilidades de base, ingresada por clínica de 2 días de evolución consistente en ictericia progresiva, episodios diarreicos sin acolia ni otra manifestación adicional. Aparentemente, su cuadro fue provocado por la administración de nimesulida, 2 tabletas al día por 2 días, contra el dolor secundario a un quiste mandibular diagnosticado en días anteriores. Durante su ingreso a urgencias la paciente describió consumo crónico, a diario desde hace 4 años, de productos de Herbalife®. Cursa con elevación de transaminasas, prolongación del tiempo de protrombina (TP) e hiperbilirrubinemia directa. Se descartan enfermedades infecciosas e inmunológicas. Se decidió iniciar el cubrimiento antibiótico y vitamina K. Finalmente y por exclusión, se realizó una biopsia hepática que sugirió un proceso inflamatorio compatible con hepatitis inducida por fármacos. La mujer evolucionó favorablemente al suspender la medicación y el suplemento dietético referido. En conclusión, el caso expuesto constituye un punto inicial en el avance hacia la investigación en hepatotoxicidad por mecanismos compartidos de diversas sustancias simultáneamente, como lo sucedido a la paciente con el uso paralelo de Herbalife® y de nimesulida.

Advances in research on small intestinal injuries caused by nonsteroidal anti-inflammatory drugs and its prevention and treatment / 中国药科大学学报

@#Nonsteroidal anti-inflammatory drugs (NSAIDs) are clinically used with common gastrointestinal adverse reactions, among which NSAIDs-induced small intestinal injuries (NSIs) are manifested in the appearance of jejunum and ileal mucosa erythema, erosion, ulcer, hemorrhage, intestinal wall perforation and obstruction et al..The pathological mechanisms of NSIs are complex, with a lack of effective prevention or treatment methods.This review summarizes the research progress of the pathological mechanisms of NSIs as well as the prevention and treatment of NSIs by misoprostol, mucosal protective agents, antibiotics and probiotics, traditional Chinese medicines and their active ingredients, nutritional supplements and other drugs in the past five years, in order to provide reference and basis for the research and development of new NSIs drugs.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 2: manifestações clínicas, fenótipos, diagnóstico e manejo / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 2: clinical features, phenotypes, diagnosis, and management

Os anti-inflamatórios não esteroidais (AINE) são os fármacos mais frequentemente associados a reações de hipersensibilidade (RH) na prática clínica. Na parte 2 dessa atualização sobre as RH aos AINE, discutiremos os aspectos clínicos dessas reações, com foco nos sinais e sintomas, como diferenciar os fenótipos clínicos, fazer a orientação desses pacientes e quando indicar procedimentos complementares, como testes cutâneos, de provocação e dessensibilização.

Nonsteroidal anti-inflammatory drugs are a major cause of drug hypersensitivity reactions in clinical practice. In this "Update Part 2", we discuss the clinical picture, including the main signs and symptoms, how to distinguish clinical phenotypes, how to manage affected patients, and when to indicate additional procedures, such as skin testing, challenge, and desensitization.

Prescripción de protectores gástricos en pacientes reumatológicos: análisis desde Consulta Externa de Gastroenterología / Prescription of gastric protectors in rheumatological patients: Analysis from a gastroenterology outpatient clinic

Introducción: Los antinflamatorios no esteroideos son los medicamentos más recetados por reumatólogos y traumatólogos. Pero a pesar de tener una eficacia similar para controlar la inflamación y el dolor, los diferentes antinflamatorios no esteroideos disponibles presentan variabilidad en su perfil de seguridad. Objetivo: Brindar una panorámica sobre la prescripción de protectores gástricos en pacientes reumatológicos, en dos centros hospitalarios, desde una perspectiva gastroenterológica. Métodos: La investigación se inscribe en el paradigma cuantitativo con un estudio observacional. Se conformaron dos grupos de pacientes, uno de ellos provenientes del hospital A y el segundo grupo pertenecía al hospital B. Discusión: Los gastroprotectores se han convertido en los fármacos de mayor demanda en las farmacias comunitarias de Ecuador, y los más prescritos son los inhibidores de la bomba de protones y en menor frecuencia los antihistamínicos H2. Respecto a los gastroprotectores más frecuentemente prescritos, según nuestro estudio, estos valores podrían obedecer a la disponibilidad y los costos de la famotidina y el omeprazol con respecto a otros medicamentos de probada eficacia (ansoprazol, pantoprazol, rabeprazol y ranitidina). Conclusiones: Durante los últimos años, el uso de los fármacos gastroprotectores en América Latina ha experimentado un importante desarrollo, con la observancia de normas y guías clínicas de manejo de casos que ofrecen recomendaciones importantes al respecto. Por tanto, desde una perspectiva gastroenterológica, para tener éxito, es indispensable procurar un conocimiento de estos aportes y evidencias científicas(AU)

Introduction: Nonsteroidal anti-inflammatory drugs are the most prescribed medications by rheumatologists and traumatologists. However, despite having similar efficacy in controlling inflammation and pain, the different available nonsteroidal anti-inflammatory drugs show variability in their safety profile. Objective: To provide an overview of the prescription of gastric protectors in rheumatological patients, in two hospital centers, from a gastroenterological perspective. Methods: The research is part of the quantitative paradigm with an observational study. Two groups of patients were formed, one of them from hospital A and the second group belonged to hospital B. Discussion: Gastroprotectors have become the drugs in greatest demand in community pharmacies in Ecuador, the most prescribed being Proton Pump Inhibitors (IBPS) and, to a lesser extent, H2 antihistamines (anti-H2). Regarding the most frequently prescribed gastroprotectors, according to our study, these values ​​could be due to the availability and costs of famotidine and omeprazole compared to other drugs with proven effectiveness, such as ansoprazol, pantoprazole, rabeprazole and ranitidine. Conclusions: In recent years, the use of gastroprotective drugs in Latin America has undergone significant development, with the observance of clinical case management norms and guidelines that offer important recommendations in this regard. Therefore, from a gastroenterological perspective, to be successful, it is essential to seek knowledge of these contributions and scientific evidence(AU)

Efectos de los antiinflamatorios no esteroideos en las tendinopatías / Effects of Non-Steroidal Anti-Inflammatory Drugs in Tendinopathies

Introducción: Los antiinflamatorios no esteroideos son comúnmente usados para el tratamiento de las tendinopatías, pero la evidencia sobre este tratamiento es escasa. Objetivo: Realizar una revisión sistemática acerca de los efectos de los en las tendinopatías. Métodos: Se desarrolló una búsqueda bibliográfica en PubMed, WOS, PEDro, Medline, Cinahl y SPORTDiscus. Se incluyeron un total de 13 ensayos clínicos con una calidad metodológica media de 7,15/10 en la escala PEDro. Conclusiones: En la mayoría de los artículos se observó una mejoría corto plazo en el dolor y la funcionalidad con el uso de AINEs. Los ensayos clínicos incluidos no analizaron la presencia de inflamación en esta patología. Se necesitan más estudios que determinen la función de la inflamación en la tendinopatía que justifique el uso de los antiinflamatorios no esteroideos(AU)

Introduction: Non-steroidal anti-inflammatory drugs are commonly used for the treatment of tendinopathies, but the evidence on this treatment is scarce. Objective: To carry out a systematic review about the effects of non-steroidal anti-inflammatory drugs in tendinopathies. Methods: A bibliographic search was carried out in PubMed, WOS, PEDro, Medline, Cinahl and SPORTDiscus. A total of 13 clinical trials with a mean methodological quality of 7.15/10 on the PEDro scale were included. Conclusions: In most of the articles, a short-term improvement in pain and functionality was observed with the use of non-steroidal anti-inflammatory drugs. The clinical trials included did not analyze the presence of inflammation in this pathology. More studies are needed to determine the role of inflammation in tendinopathy that justifies the use of nonsteroidal anti-inflammatory drugs(AU)

A prospective, multicentric study to determine the safety and effectiveness of fixed-dose combination of camylofin dihydrochloride and nimesulide in patients presenting with acute colicky abdominal pain in India

Background:Spasmolytics and NSAIDs are a therapy of choice in colic pain. However, the tolerability and effectiveness of this combination remains unexplored. The aim of this prospective, single-arm, open label, multicenter study was to evaluate the safety and effectiveness of Anafortan-N�(fixed-dose combination of camylofin dihydrochloride 50 mg + nimesulide 100 mg) in patients with acute colicky abdominal pain.Methods: In all, 295 patients with acute colicky abdominal pain and at least one episode of colicky pain in the last 24 hours were enrolled in this study. None of the patients were hospitalized. All patients were advised Anafortan-N畉ablets twice daily orally for 5 days. The safety of Anafortan-N畐as assessed by number and percentage of patients with adverse events (AEs) and change in the severity and frequency of AEs by the end of treatment. The tolerability was determined by number and percentage of patients who hadto discontinue the treatment due to AEs. The effectiveness was evaluated as percentage change in the mean intensity of pain score (based on a 100-mm visual analog scale) from baseline to end of treatment.Results: Overall, 14 (4.7%) patients reported 14 AEs, all of which were treatment-emergent and non-serious. Of the 14 AEs, 7 AEs were mild, 6 AEs were moderate, and 1 AE was severe. No serious adverse events (SAEs) were reported. No adjustment of the study medication was required in response to any of the AEs, and none of the AEs led to discontinuation of the study treatment. At end of treatment(EOT), the pain intensity significantly (p<0.0001) reduced to 1.7�49 with a mean change of -69.9�.42 from baseline, and the daily pain intensity significantly (p<0.0001) reduced to 0.1�38 with a mean change of -3.5�77 from baseline.Conclusions: Among Indian patients presenting with acute abdominal colicky pain, twice daily treatment with a FDC of camylofin dihydrochloride 50 mg and nimesulide 100 mg (Anafortan-N�) showed significant reduction in pain intensity with very few side effects, thereby confirming its safety, tolerability, and effectiveness in acute colicky abdominal pain.

Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

Anti-inflammatories for delayed onset muscle soreness: systematic review and meta-analysis / Antiinflamatorios para el dolor muscular de inicio tardío: revisión sistemática y metanálisis / Anti-inflamatórios para dor muscular de início tardio: revisão sistemática e metanálise

ABSTRACT Objective: To investigate the effectiveness of pharmacological interventions in the treatment of delayed onset muscle soreness (DOMS). Design: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Data sources: The PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs published prior to August 3, 2020. Eligibility criteria for selecting studies: Studies that 1) used an RCT design; 2) evaluated the effectiveness of steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) in treating DOMS; and 3) therapeutically used drugs after exercise were included. Results: In total, 26 studies (patients = 934) were eligible for inclusion in the qualitative analysis on the treatment of DOMS. The results of the meta-analysis showed no superiority between the use and non-use of NSAIDs in the improvement of late muscle pain, as no statistically significant differences were verified (21 studies, n= 955; standard mean difference (SMD)= 0.02; 95% confidence interval (CI) −0.58, 0.63; p=0.94; I2=93%). The quality of the synthesized evidence was very low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and there was significant heterogeneity among the included studies. Conclusion: The results demonstrate that NSAIDs are not superior to controls/placebos in treating DOMS. The inclusion of both studies with dose-response protocols and those with exercise protocols may have influenced the results. In addition, the high risk of bias identified reveals that limitations need to be considered when interpreting the results. Level of evidence I; ystematic review of RCT (Randomized and Controlled Clinical Trials).

RESUMEN Objetivo: Investigar la efectividad de las intervenciones farmacológicas en el tratamiento del dolor muscular de aparición tardía (DOMS). Metodología: Revisión sistemática y metanálisis de ensayos clínicos controlados aleatorios (RCT). Fuentes de datos: Se realizaron búsquedas en las bases de datos de PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo y Cochrane Central Register of Controlled Trials (CENTRAL) para ECA publicados antes del 3 de agosto de 2020. Criterios de elegibilidad para la selección de estudios: Estudios en los que 1) se utilizó un diseño de RCT; 2) se evaluó la eficacia de los fármacos antiinflamatorios no esteroideos (AINE) y esteroideos en el tratamiento de DOMS; y 3) se incluyó el uso terapéutico de medicamentos para dolor después del ejercicio. Resultados: En total, 26 estudios (pacientes = 934) fueron elegibles para su inclusión en el análisis cualitativo sobre el tratamiento de DOMS. Los resultados encontrados en el metanálisis no demostraron superioridad entre el uso y no uso de AINE para mejorar el dolor muscular tardío cuando se comparó con una condición de control, ya que no hubo diferencias estadísticamente significativas (21 estudios, n = 955; media estándar diferencia = 0,02; intervalo de confianza (IC) del 95% −0,58, 0,63; p = 0,94; I2 = 93%). La calidad de la evidencia encontrada se clasificó como muy baja según los criterios del "Grading of Recommendations Assessment, Development and Evaluation" (GRADE), principalmente porque existe una heterogeneidad significativa entre los estudios incluidos. Conclusión: Los resultados demuestran que los AINE no son superiores a los controles o placebos en el tratamiento de DOMS. La inclusión de ambos modelos de estudio con protocolos de dosis-respuesta y protocolos de ejercicio puede haber influido en los resultados. Además, el alto riesgo de sesgo identificado revela que la interpretación de los resultados debe verse con limitaciones. Nivel de evidencia: I; Revisión sistemática de ECRC (Ensayos clínicos aleatorizados y controlados).

RESUMO Objetivo: Investigar a eficácia das intervenções farmacológicas no tratamento da dor muscular de início tardio (DOMS). Desenho: Revisão sistemática e metanálise de estudos clínicos randomizados e controlados (RCTs). Fontes de dados: Os bancos de dados PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo e Cochrane Central Register of Controlled Trials (CENTRAL) foram pesquisados em busca de RCTs publicados antes de 3 de agosto de 2020. Critérios de elegibilidade para selecionar estudos: Estudos que 1) usaram um desenho de RCT; 2) avaliaram a eficácia de anti-inflamatórios esteroides ou não esteroides (AINEs) no tratamento de DOMS e 3) incluíram tratamento medicamentoso depois de exercício. Resultados: No total, 26 estudos (pacientes = 934) foram elegíveis para inclusão na análise qualitativa do tratamento de DOMS. Os resultados da metanálise não mostraram superioridade entre o uso e não uso de AINEs na melhora da dor muscular tardia, pois não foram verificadas diferenças estatisticamente significativas (21 estudos, n = 955; diferença média padronizada (SMD) = 0,02; Intervalo de confiança (IC) de 95% −0,58, 0,63; p = 0,94; I2 = 93%). A qualidade da evidência encontrada foi muito baixa de acordo com os critérios da Grading of Recommendations Assessment, Development and Evaluation (GRADE), e verificou-se heterogeneidade significante entre os estudos incluídos. Conclusão: Os resultados demonstram que os AINEs não são superiores aos controles ou placebos no tratamento de DOMS. A inclusão de estudos com protocolos de dose-resposta e com protocolos de exercícios podem ter influenciado os resultados. Além disso, o alto risco de viés identificado revela que as limitações devem ser consideradas na interpretação dos resultados. Nível de evidência I; Revisão sistemática de ECRC (Estudos clínicos randomizados e controlados).

Risk factors for radiological hip involvement in patients with ankylosing spondylitis

SUMMARY OBJECTIVE: Our study aimed to explore the potential risk factors for radiological hip joint involvement in patients with ankylosing spondylitis (AS). METHODS: This cross-sectional convey collected the clinical data, laboratory indicators, and radiographic data of patients with AS. Radiographic hip joint involvement was defined as a Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-hip) score ≥2. Multivariate logistic regression analyses were conducted to explore the potential risk factors for radiological hip involvement in patients with AS. RESULTS: Based on BASRI-hip score, all enrolled 386 patients with AS were classified as patients involving with radiological hip joint involvement (BASRI-hip ≥2; n=203) and those without it (BASRI-hip ≤1; n=183). Mean age of enrolled patients with AS were 36.7±11.9 years, and 320 (82.9%) patients were male. Mean course of disease was 10.7±8.3 years, and 349 (90.4%) patients were with a positive HLAB27. Multivariate analyses indicated that Juvenile onset (onset age ≤16 years) (odds ratio [OR]=4.159, 95% confidence interval [CI], 1.779-9.721, p<0.001), body mass index (BMI) <18.5 kg/m2 (OR=1.986, 95%CI 1.187-3.323, p=0.009), continuous nonsteroidal anti-inflammatory drug (NSAID) use (OR=0.351, 95%CI 0.155-0.794, p=0.012), and bone mass below the expected range for age (Z score ≤-2) (OR=2.791, 95%CI 1.456-5.352, p=0.002) were independently associated with radiological hip joint involvement in patients with AS. CONCLUSIONS: The potential risk factors for radiological hip joint involvement were juvenile onset, lower BMI, and bone mass below the expected range for age. Furthermore, continuous NSAID use was the protective factor for radiological hip joint involvement in these population.

Bleeding after tooth extraction in patients receiving anticoagulation/antiplatelet therapy / 口腔疾病防治

@#Tooth extraction in patients receiving anticoagulation/antiplatelet therapy is often considered contraindicated by many oral and maxillofacial surgeons because of a higher risk of postoperative bleeding. Multiple factors contribute to postoperative bleeding, but there is no consensus. Based on recent literature, this article reviews factors related to bleeding after tooth extraction in patients receiving anticoagulation/antiplatelet therapy. The literature review indicates that patients taking antiplatelet drugs have a lower postoperative bleeding risk than patients taking anticoagulant drugs. Prescription of anticoagulants together with non-steroidal anti-inflammatory drugs, selective serotonin inhibitors or serotonin-norepinephrine inhibitors increases the risk of bleeding, so does preoperative antibiotic use increase. In addition, systemic diseases such as diabetes, history of infection at the extraction site, and greater surgical trauma are associated with a higher risk of postoperative bleeding. At present, it is generally believed that it is safe and feasible to use different hemostatic measures after tooth extraction and to rationally apply different hemostatic measures after surgery. More prospective controlled trials are needed in the future to establish an assessment system for patients undergoing anticoagulation/antiplatelet therapy under different conditions during tooth extraction.

Brazilian recommendations for the use of nonsteroidal anti-inflammatory drugs in patients with axial spondyloarthritis

Abstract Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians' decision making, without taking out his/her autonomy when prescribing for an individual patient.(AU)

Factors Affecting Quality of Life and Satisfaction in Patients with Arthritis after Change to a Fixed-Dose Naproxen/Esomeprazole Combination Drug

BACKGROUND: In drug therapy for patients with arthritis, a naproxen/esomeprazole combination drug may be a tolerable choice because it can minimize gastrointestinal and cardiovascular adverse effects. The aim of this study was to investigate the changes in quality of life (QOL), medication adherence, and satisfaction after switch from the existing drug to the combination drug. In addition, we analyzed the correlation between the above-mentioned variables and the stratified demographic and medical data of the patients.METHODS: A prospective, noninterventional, observational study was conducted in 30 hospitals between May 2014 and July 2016. In total, 2,308 patients with osteoarthritis, 99 patients with rheumatoid arthritis, and 76 patients with ankylosing spondylitis were enrolled. Demographic information (age, sex, body mass index [BMI], alcohol consumption, and smoking) and medical information (type of arthritis, duration of disease, and comorbidities) were collected via a self-administered questionnaire. Patients were observed for more than three months after switching to the combination drug. Data on the QOL (EuroQoL 5-Dimension questionnaire [EQ-5D questionnaire]), medication adherence (Morisky Medication Adherence Scale [MMAS]), and satisfaction were collected at the first and last visits.RESULTS: A total of 2,483 patients enrolled at 30 hospitals completed the questionnaire. After the switch to the combination drug, the mean EQ-5D score improved from 0.72 ± 0.17 to 0.79 ± 0.14 (p < 0.001), and significant improvement was associated with female sex (p = 0.016), shorter disease duration (p < 0.001), and absence of comorbidities (p < 0.001). The mean MMAS score was 6.38 ± 1.77, indicating medium adherence. Satisfaction was significantly higher in female patients (p < 0.001), in patients with a shorter disease duration (p < 0.001), osteoarthritis (p = 0.003), and no comorbidities (p < 0.001). Serious drug-related adverse effects did not occur.CONCLUSIONS: The overall QOL was improved with medium adherence after the switch to the combination drug. On the basis of the analysis of stratified data, sex, age, drinking, smoking, disease duration, comorbidities, and BMI might be associated with QOL, satisfaction, and adherence.

Dosis acumulada de analgésicos no esteroides relacionada con úlcera péptica hemorrágica y sus complicaciones en una población mexicana / Cumulative dose of non-steroidal analgesics related to hemorrhagic peptic ulcer and complications in a Mexican population

Resumen: OBJETIVO: Evaluar la dosis acumulada ingerida de antiinflamatorios no esteroides (AINEs) en pacientes con úlcera péptica hemorrágica y sus complicaciones durante la hospitalización. MATERIAL Y MÉTODO: Estudio retrospectivo en el que de julio de 2015 a diciembre de 2017 se evaluaron dos grupos: uno con antecedente hospitalario de perforación, resangrado, reintervención endoscópica y muerte y otro sin complicaciones. Se ajustó la dosis ingerida de diferentes AINEs equivalente a 10 mg de ketorolaco; se registró el índice de Charlson, infección por H. pylori y la clasificación endoscópica de Forrest. RESULTADOS: Hubo 156 admisiones de úlcera péptica hemorrágica (edad promedio de 70 años, 53% hombres), las complicaciones ocurrieron en 53 (33.9%), la dosis promedio mensual de AINEs fue de 2121 mg (pacientes con complicaciones) vs 1970 mg (sin complicaciones; p = 0.2). La tasa de AINEs/semana de 7.1 se relacionó con perforación. A todos se les aplicó dosis de omeprazol de 40 mg cada 12 horas vía intravenosa durante la hospitalización. Las complicaciones se correlacionaron con mayor índice de Charlson. Hubo relación entre muerte, factores de riesgo de úlcera péptica por estrés (sepsis, traumatismo, etc.) y la administración de anticoagulantes. El tabaquismo y el género masculino se relacionaron con mayor resangrado. CONCLUSIONES: Existe mayor probabilidad de perforación con necesidad de cirugía, estancia hospitalaria más larga y mayor número de transfusiones con mayor dosis ingerida de AINEs.

Abstract: OBJECTIVE: To evaluate the cumulative dose of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with hemorrhagic peptic ulcer and their complications along hospitalization. MATERIAL AND METHOD: A retrospective study done from July 2015 to December 2017 including two groups: one with a hospitalization history of perforation, rebleeding, endoscopic reintervention and death, another group without complications. We registered doses of different NSAIDs according to 10 mg of ketorolac, Charlson index, H. pylori infection and endoscopic Forrest classification. RESULTS: There were 156 admissions of hemorrhagic peptic ulcer with the administration of NSAIDs (average age 70 years, 53% men), complications occurred in 53 (33.9%). The average monthly dose of NSAID in the cases was 2121 mg vs 1970 mg in controls. The NSAID/week rate of 7.1 was associated with perforation. Charlson index correlated with complications. Death and physiological stress related with the administration of anticoagulants. Smoking and the male gender related to higher rebleeding. CONCLUSIONS: The higher the NSAID/weekly rate, the higher the probability of perforation with the need for surgery, longer hospital stay and increased number of transfusions.

Study to Determine the Definite Percentage of the Different Analgesic Drugs and Analgesic Techniques Used At the Postoperative Ward for Pain Management in Sir Salimullah Medical College Hospital, Mitford, Dhaka

Background: The rationale of determining the percentage ofanalgesics used in postoperative period is to determine the realutilization of opioid sparing effect of nonsteroidal antiinflammatory drugs and the concept of multimodal analgesia.Objectives: To determine the cost of opioids consumptionbecause the opioids are expensive.Methods: Total 541 patients were selected to find out thetypes of analgesics are being used in the postoperative eperiod irrespective of the types of operation and anaesthesia,premedication by analgesics and intraoperative analgesicsused or not. Patients were divided into several age groups.Results: In the existing prospective cross sectional study it isviewed that combination of intramuscular injection of pethidineand nonsteroidal anti-inflammatory drugs (either in suppositoryform or intravenous or intramuscular route) have the highestpercentage in postoperative pain relief.

Efficacy of preoperative nonsteroidal anti-inflammatory drug and the re-dilation technique in minimizing miosis after femtosecond laser in cataract surgery / Eficácia do AINE pré-operatório e da técnica de re-dilatação em minimizar a miose na cirurgia de catarata com laser de femtosegundo

ABSTRACT Purpose: To assess the efficacy of using a nonste­roidal anti-inflammatory drug preoperatively and of applying the re-dilation technique when necessary to minimize pupil size variation when comparing the degree of mydriasis before femtosecond laser pretreatment with that at the beginning of phacoemulsification. Methods: This retrospective study included patients who underwent cataract surgery using the LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Our routine dilating regimen with flurbiprofen, tropicamide, and phenylephrine was used. The re-dilation technique was applied on eyes that manifested with a pupillary diameter that was smaller than the programmed capsulotomy diameter after laser pretreatment. The technique consists of overcoming pupillary contraction by instilling tropicamide and phenylephrine before phacoemulsification. Pupil size was assessed before femtosecond laser application and at the beginning of phacoemulsification. Results: Seventy-five eyes (70 patients) were included. Nine (12%) eyes underwent the re-dilation technique. There was no significant difference in mean pupillary diameter and mean pupillary area between the two studied surgical time points (p=0.412 and 0.437, respectively). The overall pupillary area constriction was 2.4 mm2. Immediately before opening the wounds for phacoemulsification, none of the eyes presented with a pupillary diameter <5 mm, and 61 (85.3%) eyes had a pupillary diameter >6 mm. Conclusion: Preoperative administration of nonsteroidal anti-inflammatory drug and the re-dilation technique resulted in no significant pupil size variation in eyes that were pretreated with the femtosecond laser, when comparing the measurements made before the laser application and at the beginning of phacoemulsification. This approach can avoid the need to proceed with cataract extraction with a constricted pupil.

RESUMO Objetivo: Avaliar a eficácia do uso de anti-inflamatório não-esteróide no pré-operatório e aplicação da técnica de re-dilatação quando necessária para minimizar a variação do tamanho pupilar ao comparar o grau de midríase antes do tra­tamento com laser de femtosegundo no início da facoemulsificação. Métodos: Esse estudo retrospectivo incluiu pacientes que foram submetidos à cirurgia de catarata usando o LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Nosso regime de di­latação de rotina com flurbiprofeno, tropicamida e fenilefrina foi usado. A técnica de re-dilatação doi aplicada em olhos que se manifestaram com um diâmetro pupilar menor do que o diâmetro da capsulotomia programado após o pré-tratamento a laser. A técnica consiste em superar a contração pupilar pela instilação de tropicamida e fenilefrina antes da facoemulsificação. O tamanho pupilar foi avaliado antes da aplicação do laser de femtosegundo e no inicio da facoemulsificação. Resultados: Setenta e cinco olhos (70 pacientes) foram incluídos. Nove (12%) olhos foram submetidos à técnica de re-dilatação. Não houve diferença significativa no diâmetro pupilar médio e na área pupilar média entre os dois tempos cirúrgicos estudados (p=0,412 e 0,437, respectivamente). A constrição global da área pupilar foi de 2,4 mm2. Imediatamente antes de abrir as incisões para a facoemulsificação, nenhum dos olhos apresentava diâmetro pupilar <5 mm e 61 (85,3%) olhos apresentavam um diâmetro pupilar >6 mm. Conclusões: O administração pré-operatória de anti-inflamatório não-esteróide e da técnica de re-dilatação resultaram em uma variação significativa do tamanho pupilar em olhos que foram pré-tratados com laser de femtosegundo, comparando as medidas realizadas antes da aplicação do laser e no inicio da facoemulsificação. Essa abordagem pode evitar a necessidade de prosseguir com a extração da catarata com uma pupila contraída.

Nonsteroidal Anti-inflammatory Drugs-sparing Effect of Symptomatic Slow-acting Drugs for Osteoarthritis in Knee Osteoarthritis Patients

OBJECTIVE: To evaluate the nonsteroidal anti-inflammatory drugs (NSAID)-sparing effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) in knee osteoarthritis (OA) patients. METHODS: A retrospective study was conducted on a cohort of knee OA patients who visited a single academic referral hospital from 2013 to 2014. Among all patients, NSAID users in their first visit were extracted and divided into SYSADOA users and SYSADOA non-users. All patients were observed from their first visit with knee OA to their last visit, NSAID discontinuation, or the date of data collection, July 2017 (mean observational periods: 369.1 days). To evaluate the NSAID-sparing effect of SYSADOA, Cox regression analysis was performed after adjusting for confounding factors. RESULTS: Patients for this study (n=212) were divided into SYSADOA users (n=57) and SYSADOA non-users (n=155). The mean age (68.8 vs. 66.6 years old, p=0.31) and the number of comorbidities (p=0.73) were comparable between the two groups. The SYSADOA users showed higher Kellgren–Lawrence (KL) grade (66.7% of patients with more than KL grade 3) than SYSADOA non-users (42.6% of patients with more than KL grade 3) (p=0.02). In treatment, the frequency of intra-articular injection was higher in the SYSADOA user group than the SYSADOA non-user group (33.3% vs. 9.0%, p<0.01). In Cox regression analysis, SYSADOA use contributed to NSAID discontinuation in knee OA patients (hazard ratio 2.97, 95% confidential interval 1.42∼6.22). CONCLUSION: This real-world analysis demonstrated that SYSADOA use combined with NSAIDs had a significant effect on NSAID discontinuation in patients with knee OA.

A Case of Zaltoprofen Induced Kounis Syndrome

Kounis syndrome is defined as the occurrence of acute coronary syndrome associated with vasoactive mediators, such as histamines in the setting of hypersensitivity and allergic reactions or anaphylactic insults. The condition can be caused by various drugs, foods, or environmental factors that cause allergic reactions. A 35-year-old male visited the emergency room with anaphylaxis accompanied by chest pain approximately 20 minutes after taking zaltoprofen, a nonsteroidal anti-inflammatory drug. After acute treatment for the anaphylaxis, the patient was stabilized and all symptoms disappeared, but the ischemic changes in the electrocardiogram and elevation of the cardiac enzymes were observed. The emergency cardiac angiography and echocardiography were all normal. The allergic reaction of this patient to zaltoprofen was believed to cause a temporary coronary arterial vasospasm, inducing Type 1 Kounis syndrome. Thus far, there have been case reports of Kounis syndrome caused by a range of nonsteroidal anti-inflammatory drugs, but there are no reports of the condition being caused by zaltoprofen. According to the pathophysiology, both cardiac and allergic symptoms must be solved simultaneously, so rapid treatment and diagnosis are needed. Doctors treating acute allergic reactions and anaphylaxis patients must check the cardiovascular symptoms thoroughly and consider the possibility of Kounis syndrome.

Double blind randomized control trial to evaluate the efficacy of ketoprofen patch to attenuate pain during venous cannulation

BACKGROUND: Venipuncture pain is an uncomfortable suffering to the patient. It creates anxiety, fear and dissatisfaction. The ketoprofen transdermal patch is a proven treatment for musculoskeletal and arthritic pain. We planned this study to evaluate the efficacy of the ketoprofen patch to reduce venipuncture pain. METHODS: Two hundred adult patients, aged 18–60 years, of either sex, ASA grade I or II, were enrolled. Presuming that therapy would decrease venipuncture pain by 30%, a power calculation with α = 0.05 and β = 0.80 required enrollment of at least 24 patients into each group. However, 100 patients in each group were recruited. Group I (Control) received a placebo patch; Group II (Ketoprofen) received a 20 mg ketoprofen patch. A selected vein on the dorsum of the patient's non-dominant hand was cannulated with 18 g intravenous cannula 1 h after the application of the respective patch. Assessment of pain was done by a 10 cm visual analogue scale (VAS) of 0–10, where 0 depicts “no pain” and 10 is “the worst imaginable pain”. The venipuncture site was assessed for the presence of skin erythema, swelling and rashes at 12 h, 24 h and at the time of decannulation. RESULTS: Incidence of pain was 100% (94/94) in the control group as compared to 93% (85/91) in the ketoprofen group. The severity of the venipuncture pain was 6 (2) and 2 (2) for control and ketoprofen groups respectively (P < 0.05). CONCLUSIONS: Application of a ketoprofen patch at the proposed site of venipuncture one hour before the attempt is effective and safe for attenuating venipuncture pain.

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation.